Process for the production of {65 -chloroacetoacetic acid esters

ABSTRACT

Esters of gamma -chloroacetoacetic acid may be prepared by reacting diketene and chlorine in the presence of a low boiling organic solvent at temperatures of -10* to - 30* C. and esterifying the reaction product while maintaining the aforementioned temperatures. This process produces yields up to 87 percent of theoretical with product purity of 97 to 98 percent.

United States Patent [151 3,666,793 Stocker et al. May 30, 1972 [54]PROCESS FOR THE PRODUCTION OF 'y-CHLOROACETOACETIC ACID ESTERSInventors: August Stocker; Karl-Josef Boosen, both of Visp, SwitzerlandAssignee: Lonza Ltd., Basel, Switzerland Filed: Apr. 22, 1969 Appl. No.:818,439

..C07c 67/00 ..660/483, 479, 544 Y [56] References Cited UNITED STATESPATENTS 2,209,683 6/1940 Boese ..260/483 Primary Examiner-James A.Patten Attorney-Christen & Sabol [57] ABSTRACT Esters of'y-chloroacetoacetic acid may be prepared by reacting diketene andchlorine in the presence of a low boiling organic solvent attemperatures of l0 to 30 C. and esterifying the reaction product whilemaintaining the aforemen tioned temperatures. This process producesyields up to 87 percent of theoretical with product purity of 97 to 98percent.

13 Claims, No Drawings PROCESS FOR THE PRODUCTION OF y-CHLOROACETOACETIC ACID ESTERS This invention relates to achloroacetoacetic acid esters lowed by esterification of the tiallyformed with alcohols.

It is known that 'y-chloroacetoacetic acid esters can be obtained bychlorinating diketene at temperatures of from to C. and esterifying'ychloroacetoacetic chloride formed with alcohols. This reaction hasadvantage when conducted in the presence of inert solvents such ascarbon tetrachloride, dichloroethane, dichloropropane or carbondisulphide. The resulting products are isolated from the reactionmixture by washing with water, drying and distilling off the solvent,followed by fractional distillation in vacuo. Crude yields of up to 73percent can be obtained in the production of the ethyl ester, whilecrude yields of up to 87 percent can be obtained in the production ofthe phenyl ester. The phenyl ester obtained by this known process is acrude product, as may be deduced from the fact that no melting point isquoted for the solid and also from the fact that only a boiling point offrom 134 to 136 C. at 8 mm Hg is quoted for the impure liquid crudeproduct.

One object of the present invention is to provide an improvedprocess forthe production of -y-chloroacetoacetic acid ester. The improvementresults in a greater yield and supression of secondary reactionsproviding purer crude products. The crude product contains approximately97 to 98 percent ychloroacetoacetic ester which, therefore, may be usedwithout purification.

The improvement of the present invention is practiced by reactingdiketene with chlorine in the presence of a low boiling solvent inert tochlorine, at temperatures from 10 to 30 C. and converting the'y-chloroacetoacetic chloride thus formed by reaction with alcohols intothe corresponding 7- chloroacetoacetic acid esters at temperatures inthe aforementioned range, whereby the alcohol employed in the secondstage being introduced at a measured rate as it is consumed. The mostfavorable temperatures for the reaction are in a range from to 25 C.,the preferred temperature being C. Temperatures higher than 10 C.promote secondary reactions, such as the formation of higherchlorinatedacetoacetic esters, while lower temperatures, i.e. temperatures below 30C., result in a great reduction in the rate of reaction.

Low boiling solvents which are suitable for present invention must beinert to chlorine chlorinated hydrocarbons such as dichloroethane,dichloropropane and carbon tetrachloride, as well as other inertsolvents such as liquid sulphur dioxide which is preferred.

Liquid sulphur dioxide is preferred because on completion of thereaction, the solvent can be removed as a gas together with the HClby-product using a water jet vacuum, and the product can be subjected todistillation if an extremely pure product is necessary.

The -y-chloroacetoacetic chloride initially formed by the reaction ofdiketene with chlorine at -30 to 10 C. is reacted with the alcoholwithout being separated from the solvent. The alcohol is introduced inmeasured quantities at such a rate that it is immediately consumedwithout ever being present in a large excess. It has proved to beparticularly advantageous to introduce the alcohol, which optionally maybe in a solution with the solvent, directly into the cooled reactionmixture and to ensure by further cooling that the temperature ismaintained between 30 and 1 0 C. Alcohols suitable for practicing thepresent invention include aliphatic alcohols such as methanol, ethanol,propanol, isopropanol, butanol, and cyclohexanol or aromatic alcoholssuch as benzyl alcohol, phenol and cresol. It must be remembered thatthe anhydrous form of the alcohols should be used.

On completion of the reaction, the reaction mixtures are washed withwater, dried for example with calcium chloride,

process for the production of 'yfrom diketene and chlorine,foly-chl0roacetoacetic chloride inipracticing the and include magnesiumsulphate and the like, and the solvents are distilled off. The desiredy-chloroacetoacetic acid esters are obtained as the residue in a need tofurther purify them before they are used, for example in theproductionof dye stuffs, pharmaceutical products and the like. The yields varyfrom 87 to 97 percent.

Although as already described there is no'need to further purify thecrude product, extremely pure esters can be obtained by fractionaldistillation in vacuo. It must be remembered to keep the vacuum as lowas possible. A vacuum of about 0.1 to 0.5 mm Hg is preferable in orderto avoid decomposition. The following specific embodiments are presentedto demonstrate the present invention.

EXAMPLE I A mixture of 500 ml of CC], and 84 g of diketene was cooled to20 C., and 71 g of chlorine gas was introduced at that temperature. 46 gof absolute'ethanol were then added dropwise with the temperaturemaintained at 20 C. Most of the HCl given off was removed in a water jetvacuum and the rest by repeated washing with water. The reaction mixturewas dried with anhydrous magnesium sulphate and the solvent distilledoff in vacuo. 150 g of 'y-chloroacetoacetic acid ethyl ester wereobtained as residue in a purity of 97 to 98 percent as determined by gaschromatography. The yield of ester was 88 percent of the theoretical,based on diketene.

EXAMPLE ll 71 g of C1 were introduced over a period of 1 hour at 25 C.into a mixture of 84 g of diketene and 100 g of liquid SO, cooled to 25C. 46 g of absolute ethanol were then added dropwise at 25 C. to 15" C.The reaction mixture was then heated with stirring to room temperatureand S0 and HCl were given off. Any residual gases were removed in awater jet vacuum. 'y-chloroacetoacetic acid ethyl ester obtainedrepresented a yield of 87 percent of the theoretical.

EXAMPLE Ill The procedure of Example 1 was followed except that 1 mol ofphenol dissolved in 100 ml of CC]; was used instead of ethanol. Removalof the solvent by distillation'left a residue consisting of 97.9 percentof y-ohloroacetoacetic acid phenyl ester. The yield of ester represented96.3 percent of the theoretical based on diketene.

Contrary to what had previously been observed the phenyl ester is acrystalline compound with a melting point of from 48 to 49 C.

The purity of the 'y-chloroacetoacetic ester products following removalof the solvent is so high that it may be used as such an intermediateproduct in the production for example of azo dyes, pharmaceuticalproducts based on pyrazolones, herbicides and plastics.

We claim:

1. A process for the chloroacetoacetic acid acid diketene and chlorineto production of esters of 7- which comprises: (a) reacting form-y-chloroacetoacetic acid chloride, said reaction being carried out at atemperature in the range of 10 to 30 C. in a reaction medium comprisedof a solvent inert to chlorine; and (b) esterifying said 7-chloroacetoacetic acid chloride with an alcohol, said esterificationbeing carried out at a temperature in the range of 10 to 30 C. in areaction medium comprised of a solvent inert to chlorine, and saidalcohol being introduced into the esterification step at a measured rateas it is consumed.

2. The process according to claim 1 wherein the reaction andesterification are conducted at a temperature of 15 to 25 C.

3. The process according to claim 1 wherein said solvent is selectedfrom the group consisting of chlorinated hydrocarbons and liquid sulfurdioxide.

4. A process according to claim 1 wherein said alcohol is selected fromthe group consisting of methanol, ethanol,

most of the HCl by-product is removed from the reaction mixture in awater jet vacuum.

10. The process according to claim 9 wherein substantially all of theremaining HCl by-product is then removed from the reaction mixture byrepeated washings with water.

11. The process according to claim 9 wherein the water is then removedfrom the reaction mixture with anhydrous magnesium sulfate.

12. The process according to claim 9 wherein the reaction medium is thendistilled off in vacuo.

13. The process according to claim 1 wherein, after step (b), the sulfurdioxide and the HCl lay-product are removed by means of a water jetvacuum.

l l l f

2. The process according to claim 1 wherein the reaction andesterification are conducted at a temperature of -15* to -25* C.
 3. Theprocess according to claim 1 wherein said solvent is selected from thegroup consisting of chlorinated hydrocarbons and liquid sulfur dioxide.4. A process according to claim 1 wherein said alcohol is selected fromthe group consisting of methanol, ethanol, propanol, isopropanol,butanol, cyclohexanol, benzol, phenol and cresol.
 5. The processaccording to claim 4 wherein said solvent is selected from the groupconsisting of dichloroethane, dichloropropane, carbon trichloride,carbon tetrachloride and liquid sulfur dioxide.
 6. The process accordingto claim 5 wherein said solvent is liquid sulfur dioxide.
 7. The processaccording to claim 6 wherein the reaction and esterification areconducted at a temperature of -15* to -20* C.
 8. The process accordingto claim 7 wherein the solvent is liquid sulfur dioxide.
 9. The processaccording to claim 1 wherein, after step (b), most of the HCl by-productis removed from the reaction mixture in a water jet vacuum.
 10. Theprocess according to claim 9 wherein substantially all of the remainingHCl by-product is then removed from the reaction mixture by repeatedwashings with water.
 11. The process according to claim 9 wherein thewater is then removed from the reaction mixture with anhydrous magnesiumsulfate.
 12. The process according to claim 9 wherein the reactionmedium is then distilled off in vacuo.
 13. The process according toclaim 1 wherein, after step (b), the sulfur dioxide and the HClby-product are removed by means of a water jet vacuum.